A major stage in the development of full-blown inhalation anthrax is the development of overwhelming bacteremia. A prominent cell type that provides protection against blood borne antigens is the marginal zone B cell. Attempts will be made to target the polyglutamate capsule and the protective antigen of anthrax to marginal zone B cells, in our proposed studies we will use mutant mice in an attempt to evaluate the role of MZ B cells in protective responses against blood-borne antigens. We will ask whether the polyglutamate capsule can be rendered immunogenic either by attempting to target it to MZ B cells, or by preserving it conformationally as a multivalent antigen. We will also examine whether the immune response to PA can be enhanced by generating a PA-C3d fusion protein or by using a PA-polysaccharide conjugate in an attempt to redirect it to MZ B cells. We will then address the general issue as to whether the reason why some antigen-C3d fusions have been successful is because the antigen was targeted to MZ B cells, using lysozyme specific B cells and lysozyme-C3d fusion proteins as a model system. We will use lysozyme-specific MZ B cells to attempt to ask what is required beyond antigen per se to initiate proliferation of antigen-specific MZ B cells. Finally we will attempt to determine whether antigen-specific MZ B cells, as opposed to follicuar B cells, can readily capture and present blood borne antigens, and thus activate na'fve T cells.